Martz_1977_J.Pharmacol.Exp.Ther_203_231

Reference

Title : Phenytoin teratogenesis: correlation between embryopathic effect and covalent binding of putative arene oxide metabolite in gestational tissue - Martz_1977_J.Pharmacol.Exp.Ther_203_231
Author(s) : Martz F , Failinger C, 3rd , Blake DA
Ref : Journal of Pharmacology & Experimental Therapeutics , 203 :231 , 1977
Abstract :

The possibility that phenytoin (DPH) teratogenesis is due to an arene oxide (epoxide) metabolite was examined. On gestational day 11, Swiss mice were given teratogenic doses of DPH (50, 75 and 100 mg/kg) with and without a nonteratogenic dose of 1,2-epoxy-3,3,3-trichloropropane (TCPO; 100 mg/kg), an epoxide hydratase inhibitor. TCPO significantly increased the incidence of DPH-induced cleft lip and palate and enhanced the embryolethality 2-fold over DPH alone. Four hours after treatment with 14C-DPH (75 mg/kg, 80-90 muCi) the covalent binding of DPH radioactivity in fetuses and placentae was enhanced 2-fold in groups cotreated with TCPO (100 mg/kg). Enhancement was still evident in placentae 24 hours after treatment. There was no effect of TCPO on maternal plasma DPH level, which was comparable to that found in clinical therapeutics (20-30 microgram/ml). Likewise, fetal and placental DPH uptake was not increased by TCPO. DPH teratogenesis is postulated to result from DPH-epoxide formation and covalent binding of epoxide, the ultimate teratogen, to constituents of gestational tissue.

PubMedSearch : Martz_1977_J.Pharmacol.Exp.Ther_203_231
PubMedID: 909055

Related information

Inhibitor Trichloropropene-oxide
Substrate Phenytoin

Citations formats

Martz F, Failinger C, 3rd, Blake DA (1977)
Phenytoin teratogenesis: correlation between embryopathic effect and covalent binding of putative arene oxide metabolite in gestational tissue
Journal of Pharmacology & Experimental Therapeutics 203 :231

Martz F, Failinger C, 3rd, Blake DA (1977)
Journal of Pharmacology & Experimental Therapeutics 203 :231